Resin anchors

Diels-Alder Reaction Using Resin-Anchored Reagents... 

The choice of protecting groups and of the type of resin-anchor required for synthesis of cyclic peptides on solid supports not only depends upon the particular amino add sequence of the target molecule, but decisively upon the mode of cyclization, particularly whether the C-terminal carboxy group should act as bridgehead or not. Correspondingly, the synthetic routes can be subdivided into two main classes either based on the attachment of the C-terminus to the solid support by suitable anchors or where side-chain functionalities are exploited for this purpose. 

The majority of cyclic peptides synthesized on solid support are cyclized in the head-to-side-chain or side-chain-to-side-chain mode. For this purpose the amino acids involved in cyclization must be side-chain protected in a manner that allows for an additional level of orthogonal deprotection. Thus, upon assembly of the fully protected linear precursor on-resin, deprotection of the functionalities involved in the lactam ring formation is performed, followed by regio-selective cyclization by amide bond formation, and finally by the resin-cleavage/deprotection step as outlined in Scheme 16. In Table 8, examples of syntheses of such cyclic peptides are listed with the relevant information regarding protection scheme, resin anchor, and mode of cyclization. 

The use of phenacyl handles 15 is only compatible with the Boc/Bzl strategy since the peptide-resin anchor is not stable to the nucleophilic conditions used in the Fmoc/tBu strategy. Besides the formation of piperazine-2,5-diones, another side reaction can take place on incorporation of the second residue. Attack by the free amino group of the first amino acid on the carbonyl group of the phenacyl resin leads to a cyclic Schiff base.P Both types of side reaction can be minimized using the in situ neutralization protocol. Photolysis is carried out as for nitrobenzyl resins. 

A number of other useful highly acid-labile handles are also available. Most of these linkers are formed by introducing electron-donating substituents into the benzyl groups that serve as the peptide-resin anchor. The first handle of this type, 4-hydroxymethyl-3-methoxyphenoxyacetic acid (HMPA), 3, was introduced by Sheppard and Williams [22,23]. A closely related and more widely used alternative is 4-(4-hydroxymethyl-3-methoxyphenoxy) butyric acid [24-26] (HMPB), 4. 

It is noteworthy that resin anchoring proceeds through the secondary alcohol of the starting scaffold. It is the only invariant part of the inhibitor... 

From determination of Val/Ala-Val on the amino acid analyzer. These values assume that all Val-resin and Ala-Val-resin anchor bonds cleave at the same rate in HBr-trifluoroacetic acid. 

Resin anchors are quite widely used already for fixing steel bars and ties in concrete and masonry structures. A concept marketed... 

Wang resin Anchor the first amino acid to the resin (0.93 mmol/g, Novabiochem, Meudon, France) according to the symmetrical anhydride method. (The standard above-mentioned procedure was applied to build the sequence.)... 

The more smoke that rolls back, the less the chance the fire can be fought safely and effectively. The rollback is often hot enough to weaken roof strata and loosen resin-anchored bolts—conditions that make travel under such questionable if not wrong, particularly if the smoke limits visibility. The rollback not only contains heat and smoke, it contains fire gases that can act like a wick, bringing flame from the fire back into firefighters. 

Resin-anchored opt-active Rh-catalyst (XXVI-XXVIII) hydrogena- tion CK-ethylstyrene, methyl-atropate opt. act. products low [88]... 

A few sihcon-containing linkers have been synthesized on sohd phase and are used to tether diverse aryl moieties without former preloading of the linker. Elhnan et aL attached aromatic and heteroaromatic compounds directly to a sihcon-substituted support for the first time. The nature of the resin anchoring of those silyl hnkers has to be chosen carefully because cleaving conditions for the release of non-alcohohc compounds may induce destruction (and therefore release) of the sihcon hnker as well. Ellman et al. synthesized a heteroatom free, masked and therefore stable silyl hnker 650 starting from allylsilanes and bromo-substituted polystyrene that can be eas-... 

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